Stem Cell Imaging Using Nanoparticles

Xarrin Sindhu

The Next Big Small thing

Stem Cell Imaging Using Nanoparticles

Nanotechnology expansive pace of progress

Tracking distribution of stem cells crucial regarding their therapeutic use

distinguishing cellular origination from a cell source

development of noninvasive techniques to trace therapeutic stem cells

A non-invasive techniqueOne such method is the use of:

superparamagnetic nanoparticles coated with polymer shell

has been used to track transplanted

stem cells.

as contrast agents for magnetic resonance (MR)

imaging

Video Demonstration

Stem cell labelling techniques

Conventional techniques

• rely on the surface attachment of magnetic beads (with size from 100 nm to m)

Latest techniques

• Super para magnetic nano particles coated with a polymer shell magnetic resonance (MR) imaging

DrawbacksConventional methods are efficient for in vitro cell separation

1

cell surface unsuitable for in vivo use due to rapid recognition and clearance of labeled cells in the reticuloendothelial system

2

New technique

short HIV-Tat peptides are used to derive super paramagnetic nanoparticles up to 10–30 pg of superparamagnetic iron per cell.

Iron incorporation does not affect cell viability, differentiation, or proliferation of CD34þ cells.

particles are efficiently internalized into hematopoietic and neural progenitor cells

tissue homed to the bone marrow and single cells could be detected by magnetoresonance imaging in the tissue samples.

Video Demonstration

Mechanism

Magnetic separation columns recover magnetically labeled cells homed to the bone marrow

Inference

Localization and retrieval of cell populations in vivo enable the detailed analysis of specific stem cell and organ interactions critical for advancing the therapeutic use of stem cells

Additional studysuperparamagnetic iron oxide nanoparticles were

fabricated and optimized to exhibit superior magnetic properties

Human neural stem cells and MSCs were labeled in vitro by using these novel particles

found to retain proliferation and differentiation

capabilities

analyzed in vitro and

Image displays the 1000s of iron oxide nanoparticles (yellow) inside a single stem cell, which ‘light up’ on MRI scans.

This technique has the potential to monitor stem cells' integration into human tumours.

So…• Super paramagnetic

iron oxide nanoparticles were fabricated and optimized to exhibit superior magnetic properties.

• Human neural stem cells and MSCs were labeled in vitro by using these novel particles, analyzed in vitro, and found to retain proliferation and differentiation capabilities

ExampleRat neural stem cells were differentiated into oligodendroglial progenitors

both lateral ventricles of myelin basic protein–deficient neonatal rats.

injected into

and

Cont’d

The cells were found in vivo by using an animal MR imaging unit for 6 weeks post transplantation.

The labeled cells were able to induce new myelin formation;

Thus, labeling by nano particles does not alter the differentiation and therapeutic potentials of stem cells

What else nano imaging offers ?

Another field of stem-cell research in which nanoparticles are used to track cells by in vivo imaging has great importance in MSC-based myocardium dysfunction therapy.

Labeled porcine MSCs retained in vitro viability and proliferation and differentiation capabilities, as well as in vivo viability after allogeneic transplantation.

Result of MSC based therapy

The labeled MSCs demonstrated useful contrast characteristics; one could distinguish labeled MSCs from unlabeled MSCs in vitro and in fresh myocardial tissue

The contrast proved satisfactory within normal or infarcted myocardium, both of which may be targeted in future MSC therapiesA minimal detectable quantity of cells (105 cells=injection) was located using conventional cardiac MR imaging, which was performed on a commercial imaging unit.

Cont’d

In this preliminary experience, the authors observed iron fluorophore particles (IFP)–containing cells with a preserved nuclear structure that had elongated and aligned with host myocardial fibers. Whether the labeled MSCs indeed migrate, differentiate, and improve myocardial function after transplantation remains to be demonstrated in longer-term studies in which careful control groups are used

Discussion

Stem cell benefitsencouraged intense interest in using these for different

therapeutic applications

But still

several problems must still be resolved before stem-cell technology can advance to the clinical

setting

HurdlesTo date, no scaffold material has been deemed optimal for

specific use in tissue engineering

stem cells on scaffolds composed of degradable fibers with nanometric diameters––fibers that resemble the collagen

fibers inhabiting the ECM

One suggestion

Copy nature’s method

Discussion

Once we have answered the questions of which scaffold and delivery vector are optimal, we will be able to:

create new tissue

However, this leads us to another question: will this newly formed tissue function in the same manner as the tissue it is supposed to replace?

To answer this, we must perform a variety of tests, including biochemical, electrophysiological, and biomechanical analyses.

Cont’d

In some research models, the newly formed tissue is too small to be examined using conventional analytical methods

Cont’d

In the analysis of new bone tissue derived from genetically engineered MSCs

nanobiomechanical analyses of other skeletal tissues as well as individual cells and ECM molecules.

Such methods can be applied

to

Prenominal

Understanding the intrinsic biomechanical parameters of engineered tissue can lead to :

optimization of the engineering process and

The production of functional tissue replacements for the skeleton.

Considerations before implants

Finally, the question of bio distribution constantly arises within the context of cell therapy.

The adverse effect of implanted cells that have found their way to distant organs rather than to the target organ should be considered in every therapeutic protocol.

What else can be done with nanoparticles?

Specific nano particles have been developed for noninvasive monitoring of cell distribution within the body.

These particles can also be used to monitor stem-cell survival post implantation

and to inform us of whether these cells are only required as inducers of tissue regeneration

or play a long-term role in the generation of new tissue.

Conclusion

Conclusion

Nanotechnologies are beginning to be implemented as analytical and production tools in stem cell–based therapeutic approaches.

Only a few tools available in the field of nanoscience have been made available to advance the use of stem cells in medicine

L'avenir

The gap between scientists traditionally involved in nanoscience and scientists dealing with biotechnology will be bridged during the coming years, leading to an increased use of nanotools in biomedicine.

The future looks bright…

We envision the application of nanotechnology in studies of:

cell–scaffold

interactions

cell–matri

x interactions

cell preservation monito

ring

Totally radical future

No doubt, this will drive stem-cell therapy closer to clinical application in human beings.